EP2226310B1 - Verfahren zur herstellung von 2-(1-hydroxyalkyl)cycloalkanon - Google Patents

Verfahren zur herstellung von 2-(1-hydroxyalkyl)cycloalkanon Download PDF

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EP2226310B1
EP2226310B1 EP08868514A EP08868514A EP2226310B1 EP 2226310 B1 EP2226310 B1 EP 2226310B1 EP 08868514 A EP08868514 A EP 08868514A EP 08868514 A EP08868514 A EP 08868514A EP 2226310 B1 EP2226310 B1 EP 2226310B1
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cycloalkanone
water
mol
reaction
reaction mixture
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EP2226310A4 (de
EP2226310A1 (de
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Junko Ueda
Yoshiharu Ataka
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Kao Corp
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Kao Corp
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups

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  • the present invention relates to a process for producing 2-(1-hydroxyalkyl)cycloalkanones.
  • Patent Document 3 it is suggested that a water layer formed in an aldol condensation reaction can be reused.
  • this method in order to reuse the water layer, it is required to once neutralize the resulting reaction mixture by adding an acid thereto and separate the thus neutralized reaction mixture into the water layer and an organic layer to remove the organic layer from the water layer, followed by adding a base catalyst to the thus separated water layer to render the water layer basic.
  • FIG. 1 is an explanatory view conceptually showing an example of the production process according to the present invention.
  • the present invention relates to a process for continuously producing a 2-(1-hydroxyalkyl)cycloalkanone while suppressing reduction in a yield thereof.
  • the present inventors have found such a process for producing a 2-(1-hydroxyalkyl)cycloalkanone in which when conducting the step of dropping and mixing a mixed solution of a cycloalkanone and an alkyl aldehyde in an aqueous solution of a base catalyst while withdrawing the resulting reaction mixture out of the reaction system, an additional amount of water containing the base catalyst is added to the reaction system in order to maintain a constant concentration of the base catalyst and/or a constant amount of water in the reaction system to thereby allow an aldol condensation reaction between the cycloalkanone and the alkyl aldehyde to proceed in a continuous manner.
  • the present inventors have found that in order to carry out the aldol condensation reaction in a continuous manner, when separating the reaction mixture withdrawn out of the reaction system into an organic layer and a water layer and then recovering and reusing the thus separated water layer in the reaction system, it is required to continuously add the base catalyst to the reaction system to compensate a loss of the base catalyst because the base catalyst tends to be converted into a neutralized salt by the reaction with a small amount of an alkyl carboxylic acid contained in the alkyl aldehyde as a raw material, and therefore deactivated.
  • the present inventors have found that since the concentration and amount of the base catalyst in the reaction system can be kept constant by continuously adding the water containing the base catalyst to the reaction system, it is possible to suppress decrease in the reaction rate as well as deactivation of the base catalyst, so that the aldol condensation reaction is allowed to proceed substantially semi-permanently and the 2-(1-hydroxyalkyl)cycloalkanone as the aimed compound can be produced with a high efficiency in a continuous manner.
  • the present invention relates to a process for producing a 2-(1-hydroxyalkyl)cycloalkanone by subjecting a cycloalkanone and an alkyl aldehyde to aldol condensation in the presence of water and a base catalyst, which includes the following steps (i) to (iii):
  • the 2-(1-hydroxyalkyl)cycloalkanone can be continuously produced while suppressing reduction in a yield thereof.
  • FIG. 1 is an explanatory view conceptually showing a preferred embodiment of the production process according to the present invention.
  • a reactor serves for subjecting a cycloalkanone, and an alkyl aldehyde which are continuously added thereto and mixed therein, to aldol condensation reaction in the presence of water and a base catalyst.
  • the reactor is continuously supplied with the cycloalkanone and the alkyl aldehyde as well as the water containing the base catalyst.
  • the reaction mixture obtained in the reactor is continuously withdrawn therefrom and introduced into a separator in which the reaction mixture is then separated into an organic layer and a water layer.
  • the cycloalkanone and the alkyl aldehyde are continuously added to the reactor in the presence of water and the base catalyst to form a reaction system.
  • the reaction system the cycloalkanone and the alkyl aldehyde are subjected to aldol condensation reaction.
  • the reactor used in the step (i) is not particularly limited as long as the reactor is provided with feed ports for the cycloalkanone, the alkyl aldehyde, water, the base catalyst or the like, a discharge port for withdrawing the reaction mixture therethrough, and other ports for the water layer reused, etc.
  • the reactor there may be used a reactor of a stirring vessel type.
  • the temperature used in the above reaction is not particularly limited, and is preferably from -5 to 40°C and more preferably from -5 to 30°C, for example, for the purposes of preventing solidification of the water layer and suppressing production of by-products such as a dimer of the cycloalkanone.
  • the pressure used in the aldol condensation reaction is preferably from 10 kPa to 1 MPa in terms of an absolute pressure, and more preferably from 50 to 300 kPa and still more preferably from 80 to 120 kPa, from the viewpoint of inexpensiveness of apparatuses used thereunder.
  • the cycloalkanone used in the present invention includes cycloalkanones having 4 to 8 carbon atoms. Among these cycloalkanones, preferred are cyclopentanone and cyclohexanone, and more preferred is cyclopentanone.
  • alkyl aldehyde used in the present invention, those aldehydes preferably containing an alkyl group having 1 to 15 carbon atoms, more preferably an alkyl group having 1 to 8 carbon atoms and still more preferably an alkyl group having 3 to 5 carbon atoms are preferred, and the aldehyde containing a straight-chain alkyl group having 4 carbon atoms is most preferred.
  • the aldehydes containing an alkyl group having 3 to 5 carbon atoms include butyraldehyde, isobutyraldehyde, valeraldehyde, isovaleraldehyde and hexylaldehyde, and the aldehyde containing a straight-chain alkyl group having 4 carbon atoms is valeraldehyde.
  • the cycloalkanone to be reacted is preferably added in an excessive amount relative to the alkyl aldehyde.
  • the amount of the cycloalkanone added is preferably from 2 to 6 mol, more preferably from 3 to 5 mol and still more preferably from 3 to 4 mol per 1 mol of the alkyl aldehyde.
  • the cycloalkanone and the alkyl aldehyde may be supplied by (i) the method of previously mixing the cycloalkanone, and the alkyl aldehyde, or (ii) the method of adding the cycloalkanone and the alkyl aldehyde separately from each other. Among these methods, preferred is the method (i).
  • the base catalyst used in the present invention is not particularly limited.
  • suitable base catalyst include those compounds represented by the following formula (7).
  • M is an alkali metal such as Li, Na and K, or an alkali earth metal such as Mg, Ca and Ba.
  • alkali metals in order to attain a good reaction efficiency, preferred are alkali metals.
  • the symbol m is an integer of 1 or 2.
  • the amount of the base catalyst used in the reaction system is preferably adjusted to from 0.005 to 0.5 mol, more preferably from 0.01 to 0.1 mol and still more preferably from 0.02 to 0.08 mol per 1 mol of the alkyl aldehyde added in terms of an amount per unit time, from the viewpoints of suppressing occurrence of side reactions and enhancing the reaction rate.
  • the amount of water being present in the reaction system is important to determine a concentration of the base catalyst in the reaction system.
  • the amount of water being present in the reaction system is controlled such that the concentration of the base catalyst in the reaction system is preferably from 0.1 to 3% by mass, more preferably from 0.5 to 2.5% by mass and still more preferably from 0.8 to 2% by mass on the basis of a total amount of water and the base catalyst contained in the reaction system.
  • the reaction between the cycloalkanone and the alkyl aldehyde may be carried out in a solvent.
  • a solvent suitable for such a two-layer reaction system is not particularly limited as long as it is inert to the aldol condensation reaction and unless it adversely affects separation and purification of the aimed compound according to the present invention.
  • the solvent include those having a boiling point of from about 140 to about 210°C, e.g., aromatic hydrocarbon solvents such as benzene and toluene; and aliphatic hydrocarbon solvents such as nonane, decane and undecane.
  • the preferred 2-(1-hydroxyalkyl)cycloalkanone obtained by the aldol condensation reaction according to the present invention includes those compounds represented by the following general formula (1).
  • n is an integer of 1 or 2, and is preferably 1.
  • R 1 is a hydrogen atom or an alkyl group having 1 to 8 carbon atoms, preferably a straight-chain or branched alkyl group having 3 to 5 carbon atoms and more preferably a straight-chain alkyl group having 4 carbon atoms.
  • an alkylidene cycloalkanone which is a dehydrated product of the 2-(1-hydroxyalkyl)cycloalkanone is also produced.
  • the dehydrated product thus produced is also useful as an intermediate product for synthesis of physiologically active substances and perfume materials similarly to the 2-(1-hydroxyalkyl)cycloalkanone.
  • the reaction mixture obtained in the step (i) is continuously withdrawn out of the reaction system while allowing the step (i) to proceed.
  • the term "while allowing the step (i) to proceed” as used herein is intended to involve the condition in which the withdrawal of the reaction mixture is conducted simultaneously with initiation of the step (i), the condition in which the withdrawal of the reaction mixture is conducted during proceeding of the step (i), or the like.
  • the aimed compound can be continuously produced with a higher productivity as compared to batch-type processes in which each reaction must be independently and separately conducted.
  • the amount of the reaction mixture withdrawn is preferably adjusted such that the total amount of the cycloalkanone and the alkyl aldehyde added to the reaction system in the step (i) is substantially identical to the amount of the organic layer in the reaction mixture withdrawn.
  • the amount of the reaction mixture withdrawn is preferably from 1 to 2.5 times, more preferably from 1 to 2 times and still more preferably from 1.2 to 2 times the total amount of the cycloalkanone and alkyl aldehyde added to the reaction system in terms of a volume ratio therebetween.
  • an additional amount of water containing the base catalyst is added to the reaction system in order to maintain a constant concentration of the base catalyst and/or a constant amount of water in the reaction system, preferably both a constant concentration of the base catalyst and a constant amount of water in the reaction system, while allowing the step (ii) to proceed.
  • the term "while allowing the step (ii) to proceed” as used herein is intended to involve the condition in which the addition of the water containing the base catalyst to the reaction system is conducted simultaneously with initiation of the step (ii), the condition in which the addition of the water containing the base catalyst to the reaction system is conducted during proceeding of the step (ii), or the like.
  • the alkyl aldehyde used in the present invention may sometimes contain an alkyl carboxylic acid as an oxidized compound of the alkyl aldehyde.
  • the base catalyst added to the reaction system in the step (iii) is used to compensate an amount of the base catalyst consumed by the reaction with the alkyl carboxylic acid, i.e., in order to maintain a constant concentration of the base catalyst in the reaction system.
  • the amount of the base catalyst added to the reaction system in the step (iii) may be identical to such an amount which is capable of compensating the amount of the base catalyst thus consumed.
  • the amount of the base catalyst added to the reaction system in the step (iii) is almost the same as the number of moles of valeric acid contained in valeraldehyde as the raw material which is determined by measuring an acid value of the valeraldehyde.
  • the amount of water added to the reaction system in the step (iii) is almost the same as the amount of water which is dissolved in the organic layer and withdrawn together with the organic layer from the reaction system.
  • the base catalyst may be added merely in an amount enough to compensate the above amount of the base catalyst consumed by the reaction with the alkyl carboxylic acid contained in the alkyl aldehyde, which results in reduction in amount of the base catalyst to be added.
  • the addition of the water containing the base catalyst to the reaction system may be carried out by adding an aqueous base catalyst solution prepared by previously dissolving the base catalyst in water, to the reaction system.
  • the reaction mixture withdrawn in the step (ii) is separated into the organic layer and the water layer, and the thus separated water layer is reused.
  • the production process of the present invention preferably further includes the above step (iv) from the viewpoints of reducing an amount of waste water discharged and reusing the cycloalkanone contained in the water layer.
  • the water layer separated by the separator is recycled to the reaction system and reused therein.
  • the production process of the present invention preferably further includes the step (v) of subjecting the organic layer separated in the step (iv) to distillation to recover the cycloalkanone contained in the organic layer and then reuse the cycloalkanone in the reaction system.
  • the cycloalkanone used in an excessive amount partially remains unreacted and contained in the organic layer. Therefore, such an unreacted cycloalkanone is recovered from the organic layer by distillation and reused in the reaction system to thereby enhance a production efficiency.
  • water contained in the organic layer may also be recovered therefrom and reused in the reaction system.
  • An alkyl(3-oxo-2-alkylcycloalkyl)acetate represented by the following general formula (5) (hereinafter referred to merely as a "compound (5)”) is a useful compound as a perfume material and a physiologically active substances, and can be obtained from the compound (1) produced by the production process of the present invention as described above.
  • n and R 1 are the same as defined above, and R 2 is an alkyl group having 1 to 3 carbon atoms, and is preferably a methyl group.
  • the method for producing the compound (5) is not particularly limited.
  • the compound (5) may be produced by the following method.
  • the compound (1) is subjected to dehydration reaction to obtain a 2-(alkylidene)cycloalkanone represented by the following general formula (2) (hereinafter referred to merely as a "compound (2)").
  • the thus obtained compound (2) is subjected to isomerization reaction in n-butanol under reflux in the presence of an aqueous acid such as hydrochloric acid and hydrobromic acid to obtain a 2-(alkyl)cycloalkenone represented by the following general formula (3) (hereinafter referred to merely as a "compound (3)").
  • n, R 1 and R 2 are the same as defined above.
  • the two R 2 groups may be the same or different from each other.
  • the base catalyst used in the reaction between the compounds (3) and (4) is not particularly limited.
  • the base catalyst include alkali metals such as sodium and potassium; and alkali metal alkoxides such as sodium alkoxides and potassium alkoxides.
  • the amount of the base catalyst used in the reaction is preferably from 0.005 to 0.2 mol per 1 mol of the compound (3).
  • the reaction between the compounds (3) and (4) is preferably carried out in a polar solvent such as alcohols.
  • the reaction temperature is preferably from -10 to 30°C and more preferably from 0 to 20°C.
  • the thus obtained compound (8) is then reacted with water to produce the compound (5).
  • water is preferably added dropwise.
  • the amount of water added is preferably from 1 to 3 mol per 1 mol of the compound (8) to be reacted therewith.
  • the reaction temperature is preferably from 150 to 250°C.
  • n and R 1 are the same as defined above.
  • the compound (6) may be produced by the following method.
  • the compound (1) is subjected to dehydration reaction to obtain the compound (2).
  • the thus obtained compound (2) is subjected to isomerization reaction in the presence of an aqueous acid such as hydrochloric acid and hydrobromic acid in n-butanol under reflux to obtain the compound (3).
  • an aqueous acid such as hydrochloric acid and hydrobromic acid in n-butanol under reflux
  • the thus obtained compound (3) is reduced with hydrogen in the presence of a catalyst such as Pd/C to obtain a compound (9) represented by the following general formula (9).
  • n and R 1 are the same as defined above.
  • a 100 mL four-necked flask was charged with 16.6 g (0.92 mol) of water and 0.16 g (0.004 mol) of sodium hydroxide. After cooling the contents of the flask to 15°C under stirring, a mixed solution containing 61.3 g (0.71 mol) of valeraldehyde (acid value: 1.5 mg-KOH/g) and 237.8 g (2.83 mol) of cyclopentanone, and 36.0 g of a sodium hydroxide aqueous solution (concentration of sodium hydroxide: 0.36% by mass) were added dropwise into the flask over 6 h.
  • the resulting reaction mixture was withdrawn from the flask at a rate 1.4 times the dropping rate, and introduced into a dropping funnel (separator) to separate the reaction mixture into an organic layer and a water layer.
  • the water layer separated as a lower layer of the reaction mixture was returned to the flask.
  • the organic layer separated as an upper layer of the reaction mixture was collected every one hour, and each part of the organic layer collected every one hour was subjected to gas chromatography.
  • the reaction mixture in the flask was separated into the respective layers, and each of the thus separated organic and water layers was analyzed by gas chromatography.
  • the organic layer contained 3.06 g (0.036 mol) of valeraldehyde, 106.5 g (0.63 mol) of 2-(1-hydroxy-n-pentyl)cyclopentanone and 2.13 g (0.014 mol) of pentylidene cyclopentanone (conversion rate of valeraldehyde: 95.0%; yield: 89.9%).
  • a 200 mL four-necked flask was charged with 33.0 g (1.83 mol) of water and 0.64 g (0.02 mol) of sodium hydroxide. After cooling the contents of the flask to 5°C under stirring, a mixed solution containing 123.6 g (1.44 mol) of valeraldehyde (acid value: 1.5 mg-KOH/g) and 482.2 g (5.73 mol) of cyclopentanone, and 56.4 g of a sodium hydroxide aqueous solution (concentration of sodium hydroxide: 0.22% by mass) were added dropwise into the flask over 6 h.
  • the resulting reaction mixture was withdrawn from the flask at a rate 1.7 times the dropping rate, and introduced into a dropping funnel to separate the reaction mixture into an organic layer and a water layer.
  • the water layer separated as a lower layer of the reaction mixture was returned to the flask.
  • the organic layer separated as an upper layer of the reaction mixture was collected every 0.5 hour, and each part of the organic layer collected every 0.5 hour was subjected to gas chromatography.
  • the reaction mixture in the flask was separated into the respective layers, and each of the thus separated organic and water layers was analyzed by gas chromatography.
  • composition of the organic layer withdrawn during an initial stage of dropping of the mixed solution was substantially identical to the composition of the organic layer withdrawn during a late stage of dropping of the mixed solution (between the 5th hour and the 6th hour) similarly to Example 1, and the reaction therefore proceeded in a stable manner.
  • the organic layer contained 4.87 g (0.057 mol) of valeraldehyde, 211.8 g (1.24 mol) of 2-(1-hydroxy-n-pentyl)cyclopentanone and 4.20 g (0.028 mol) of pentylidene cyclopentanone, and the conversion rate of valeraldehyde and the yield of the aimed product were 96.0% and 88.9%, respectively.
  • composition of the organic layer withdrawn during an initial stage of dropping of the mixed solution was substantially identical to the composition of the organic layer withdrawn during a late stage of dropping of the mixed solution (between the 5th hour and the 6th hour) similarly to Example 1, and the reaction therefore proceeded in a stable manner.
  • a 200 mL four-necked flask was charged with 33.0 g (1.83 mol) of water and 0.63 g (0.02 mol) of sodium hydroxide. After cooling the contents of the flask to 5°C under stirring, a mixed solution containing 123.2 g (1.43 mol) of valeraldehyde (acid value: 1.5 mg-KOH/g) and 241.2 g (2.87 mol) of cyclopentanone, and 35.5 g of a sodium hydroxide aqueous solution (concentration of sodium hydroxide: 0.37% by mass) were added dropwise into the flask over 6 h.
  • the resulting reaction mixture was withdrawn from the flask at a rate 2.1 times the dropping rate, and introduced into a dropping funnel to separate the reaction mixture into an organic layer and a water layer.
  • the water layer separated as a lower layer of the reaction mixture was returned to the flask.
  • the organic layer separated as an upper layer of the reaction mixture was collected every 0.5 hour, and each part of the organic layer collected every 0.5 hour was subjected to gas chromatography.
  • the reaction mixture in the flask was separated into the respective layers, and each of the thus separated organic and water layers was analyzed by gas chromatography.
  • the organic layer contained 10.09 g (0.12 mol) of valeraldehyde, 191.7 g (1.13 mol) of 2-(1-hydroxy-n-pentyl)cyclopentanone and 5.94 g (0.039 mol) of pentylidene cyclopentanone and the conversion rate of valeraldehyde and the yield of the aimed product were 91.8% and 81,5%, respectively.
  • composition of the organic layer withdrawn during an initial stage of dropping of the mixed solution was substantially identical to the composition of the organic layer withdrawn during a late stage of dropping of the mixed solution (between the 5th hour and the 6th hour) similarly to Example 1, and the reaction therefore proceeded in a stable manner.
  • a 100 mL four-necked flask was charged with 16.6 g (0.92 mol) of water and 0.16 g (0.004 mol) of sodium hydroxide. After cooling the contents of the flask to 15°C under stirring, a mixed solution containing 165.3 g (1.92 mol) of valeraldehyde (acid value: 1.5 mg-KOH/g) and 646.4 g (7.68 mol) of cyclopentanone, and 95.1 g of a sodium hydroxide aqueous solution (concentration of sodium hydroxide: 0.35% by mass) were added dropwise into the flask over 16 h.
  • the resulting reaction mixture was withdrawn from the flask at a rate 1.4 times the dropping rate, and introduced into a dropping funnel to separate the reaction mixture into an organic layer and a water layer.
  • the water layer separated as a lower layer of the reaction mixture was returned to the flask.
  • the organic layer separated as an upper layer of the reaction mixture was collected every 1 hour, and each part of the organic layer collected every 1 hour was subjected to gas chromatography.
  • the reaction mixture in the flask was separated into the respective layers, and each of the thus separated organic and water layers was analyzed by gas chromatography.
  • the organic layer contained 11.88 g (0.14 mol) of valeraldehyde, 278.1 g (1.63 mol) of 2-(1-hydroxy-n-pentyl)cyclopentanone and 5.8 g (0.038 mol) of pentylidene cyclopentanone, and the conversion rate of valeraldehyde and the yield of the aimed product were 92.8% and 87. 1%, respectively.
  • compositional ratios of the main components of the organic layer with time are shown in Table 1. As a result, as shown in Table 1, it was confirmed that even when the reaction was continuously carried out for the period as long as 16 h, the reaction still proceeded in a stable manner.
  • a 200 mL four-necked flask was charged with 50.0 g (2.78 mol) of water and 0.48 g (0.012 mol) of sodium hydroxide. After cooling the contents of the flask to 15°C under stirring, a mixed solution containing 59.7 g (0.69 mol) of valeraldehyde (acid value: 1.5 mg-KOH/g) and 237.9 g (2.83 mol) of cyclopentanone was added dropwise into the flask over 2 h. While dropping, the resulting reaction mixture was withdrawn from the flask at the same rate as the dropping rate, and introduced into a dropping funnel to separate the reaction mixture into an organic layer and a water layer.
  • the water layer separated as a lower layer of the reaction mixture was returned to the flask. After completion of dropping the mixed solution, the reaction mixture in the flask was separated into the respective layers, and each of the thus separated organic and water layers was analyzed by gas chromatography. As a result, it was confirmed that the organic layer contained 2.10 g (0.024 mol) of valeraldehyde, 101.6 g (0.60 mol) of 2-(1-hydroxy-n-pentyl)cyclopentanone and 1.91 g (0.013 mol) of pentylidene cyclopentanone, and the conversion rate of valeraldehyde and the yield of the aimed product were 96.5% and 88.0%, respectively.
  • a 200 mL four-necked flask was charged with 27.2 g of the water layer obtained in Comparative Example 1-1 and 27.9 g (1.55 mol) of water. After cooling the contents of the flask to 15°C under stirring, a mixed solution containing 59.6 g (0.69 mol) of valeraldehyde (acid value: 1.5 mg-KOH/g) and 237.8 g (2.83 mol) of cyclopentanone was added dropwise into the flask over 2 h. While dropping, the resulting reaction mixture was withdrawn from the flask at the same rate as the dropping rate, and introduced into a dropping funnel to separate the reaction mixture into an organic layer and a water layer.
  • the water layer separated as a lower layer of the reaction mixture was returned to the flask. After completion of dropping the mixed solution, the reaction mixture in the flask was separated into the respective layers, and each of the thus separated organic and water layers was analyzed by gas chromatography. As a result, it was confirmed that the organic layer contained 3.79 g (0.044 mol) of valeraldehyde, 98.3 g (0.58 mol) of 2-(1-hydroxy-n-pentyl)cyclopentanone and 1.62 g (0.011 mol) of pentylidene cyclopentanone, and the conversion rate of valeraldehyde and the yield of the aimed product were 93.6% and 86.0%, respectively.
  • a 200 mL four-necked flask was charged with 28.0 g of the water layer obtained in Comparative Example 1-2 and 28.2 g (1.56 mol) of water. After cooling the contents of the flask to 15°C under stirring, a mixed solution containing 59,0 g (0.68 mol) of valeraldehyde (acid value: 1.5 mg-KOH/g) and 237.8 g (2.83 mol) of cyclopentanone was added dropwise into the flask over 2 h. While dropping, the resulting reaction mixture was withdrawn from the flask at the same rate as the dropping rate, and introduced into a dropping funnel to separate the reaction mixture into an organic layer and a water layer.
  • the water layer separated as a lower layer of the reaction mixture was returned to the flask. After completion of dropping the mixed solution, the reaction mixture in the flask was separated into the respective layers, and each of the thus separated organic and water layers was analyzed by gas chromatography. As a result, it was confirmed that the organic layer contained 9.77 g (0.11 mol) of valeraldehyde, 85.8 g (0.50 mol) of 2-(1-hydroxy-n-pentyl)cyclopentanone and 1.14 g (0.008 mol) of pentylidene cyclopentanone, and the conversion rate of valeraldehyde and the yield of the aimed product were 83.4% and 74,8%, respectively.
  • the water layer separated as a lower layer of the reaction mixture was returned to the flask. After completion of dropping the mixed solution, the reaction mixture in the flask was separated into the respective layers, and each of the thus separated organic and water layers was analyzed by gas chromatography. As a result, it was confirmed that the organic layer contained 43.5 g (0.51 mol) of valeraldehyde, 25.4 g (0.15 mol) of 2-(1-hydroxy-n-pentyl)cyclopentanone and 0.21 g (0.001 mol) of pentylidene cyclopentanone, and the conversion rate of valeraldehyde and the yield of the aimed product were 26.2% and 22.0%, respectively.

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Claims (7)

  1. Verfahren zur Herstellung eines 2-(1-Hydroxyalkyl)cycloalkanons, indem ein Cycloalkanon und ein Alkylaldehyd in Gegenwart von Wasser und einem Basenkatalysator einer Aldolkondensation unterzogen werden, worin das Verfahren die folgenden Schritte (i) bis (iii) umfasst:
    Schritt (i): kontinuierliches Mischen des Cycloalkanons und des Alkylaldehyds in Wasser und dem Basenkatalysator, um ein Reaktionssystem zu bilden und es den beiden Verbindungen zu ermöglichen, miteinander zu reagieren;
    Schritt (ii): kontinuierliches Entfernen der in Schritt (i) gebildeten Reaktionsmischung aus dem Reaktionssystem, während es ermöglicht wird, dass Schritt (i) fortschreitet; und
    Schritt (iii): Hinzufügen einer weiteren Menge von Wasser, das den Basenkatalysator enthält, in das Reaktionssystem, um eine konstante Konzentration des Basenkatalysators und/oder eine konstante Menge an Wasser im Reaktionssystem aufrechtzuerhalten, während es ermöglicht wird, dass der Schritt (ii) fortschreitet.
  2. Verfahren gemäß Anspruch 1, das weiterhin den Schritt (iv) des Auftrennens der in Schritt (ii) entfernten Reaktionsmischung in eine organische Schicht und eine Wasserschicht umfasst, um die Wasserschicht erneut zu verwenden.
  3. Verfahren gemäß Anspruch 2, das weiterhin den Schritt (v) des Durchführens einer Destillation der in Schritt (iv) abgetrennten organischen Schicht umfasst, um das in der organische Schicht enthaltene Cycloalkanon zurückzugewinnen und dann das Cycloalkanon im Reaktionssystem erneut zu verwenden.
  4. Verfahren gemäß irgendeinem der Ansprüche 1 bis 3, worin das Cycloalkanon in einer Menge von 2 bis 6 Mol pro 1 Mol des hinzugefügten Alkylaldehyds hinzugefügt wird.
  5. Verfahren gemäß irgendeinem der Ansprüche 1 bis 4, worin die Menge der entfernten Reaktionsmischung vom 1- bis 2,5-fachen der Gesamtmenge des hinzugefügten Cycloalkanons und Alkylaldehyds, bezogen auf ein Volumenverhältnis zwischen diesen, ist.
  6. Verfahren gemäß irgendeinem der Ansprüche 1 bis 5, worin die Reaktion im Schritt (i) bei einer Temperatur von -5 bis 40°C durchgeführt wird.
  7. Verfahren gemäß irgendeinem der Ansprüche 1 bis 6, worin das 2-(1-Hydroxyalkyl)cycloalkanon eine Verbindung der folgenden allgemeinen Formel (1) ist:
    Figure imgb0009
     worin n eine ganze Zahl von 1 oder 2 ist; und R1 ein Wasserstoffatom oder eine Alkylgruppe mit 1 bis 8 Kohlenstoffatomen ist.
EP08868514A 2007-12-28 2008-12-22 Verfahren zur herstellung von 2-(1-hydroxyalkyl)cycloalkanon Active EP2226310B1 (de)

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